L-citrulline catabolism in Klebsiella michiganensis M5al
Best path
AO353_03055, AO353_03050, AO353_03045, AO353_03040, arcB, arcC, odc, puuA, puuB, puuC, puuD, gabT, gabD
Also see fitness data for the top candidates
Rules
Overview: Citrulline can be catabolized via ornithine carbamoyltransferase in reverse (PMID:3129535). Genetic evidence suggests that some bacteria use a putative citrullinase (EC 3.5.1.20) to consume citrulline.
- all:
- citrulline-transport, arcB, arcC and ornithine-degradation
- or citrulline-transport, citrullinase and ornithine-degradation
- Comment: Citrulline is coverted to ornithine by ornithine carbamoyltransferase (arcB) in reverse; the carbamoyltransferase reaction also yields carbamoyl-phosphate, which is consumed by carbamate kinase (arcC) in reverse. Alternatively, a putative citrullinase hydrolyzes citrulline; the product is probably ornithine.
- ornithine-degradation:
- aruF, aruG, astC, astD and astE
- or rocD and rocA
- or rocD, PRO3 and proline-degradation
- or ocd and proline-degradation
- or odc and putrescine-degradation
- or orr, oraS, oraE, ord, ortA and ortB
- Comment: Ornithine is a common intermediate. It can be succinylated by aruFG and then catabolized by the later steps of the arginine succinyltransferase pathway, via aminotransferase, dehydrogenase, and desuccinylase reactions (see PMC179677 and PMID:7523119). Or as part of L-arginine degradation I, the aminotransferase rocD converts ornithine to glutamate 5-semialdehyde, which spontaneously converts to 1-pyrroline-5-carboxylate. A dehydrogenase converts this to glutamate. Or 1-pyrroline-5-carboxylate can be reduced to proline by PRO3, as in L-arginine degradation VI. Alternatively, ornithine can be converted directly to proline by ornithine cyclodeaminase (ocd). Or ornithine can be decarboxylated to putrescine by odc (link). Or ornithine can be catabolized via D-ornithine, as in L-arginine degradation XIV. A racemase converts L-ornithine to D-ornithine; an aminomutase forms (2R,4S) 2,4-diaminopentanoate; a dehydrogenase forms (2R)-2-amino-4-oxopentanoate, and a thiolase cleaves it to D-alanine and acetyl-CoA. D-alanine could be oxidized to pyruvate or perhaps secreted; this is not described here.
- proline-degradation:
- put1 and putA
- or prdF, D-proline-reductase and 5-aminovalerate-degradation
- Comment: In pathway I, proline dehydrogenase (put1) forms (S)-1-pyrroline-5-carboxylate, which spontaneously hydrates to L-glutamate 5-semialdehyde, and a dehydrogenase (putA) to glutamate. Glutamate can be transaminated to 2-oxoglutarate, which is an intermediate in central metabolism (not represented). In pathway II, proline racemase (prdF) forms D-proline, and a reductase forms 5-aminovalerate.
- D-proline-reductase: prdA, prdB and prdC
- Comment: D-proline reductase includes components PrdA and PrdB and electron transfer protein PrdC
- 5-aminovalerate-degradation: davT, davD and glutarate-degradation
- Comment: 5-aminovalerate is an intermediate in L-lysine degradation (link, link). It is transaminated to glutarate semialdehyde and oxidized to glutarate. (A fermentative pathway via 5-hydroxyvalerate has also been reported, but does not seem to be fully linked to sequence; see pathway 5 of PMID:11759672.)
- glutarate-degradation:
- glaH and lhgD
- or gcdG and glutaryl-CoA-degradation
- Comment: Glutarate is an intermediate in L-lysine degradation. As part of MetaCyc pathway L-lysine degradation I (link), gluratate is hydroxylated to L-2-hydroxyglutarate (also known as (S)-2-hydroxyglutarate) by a 2-oxoglutarate-dependent oxidase. This reaction releases succinate (a TCA cycle intermediate) and CO2. A dehydrogenase then oxidizes to L-2-hydroxyglutarate to regenerate 2-oxoglutarate. Alternatively, as part of pathway IV (link), glutarate can be activated to glutaryl-CoA by a CoA-transferase. Glutaryl-CoA degradation (link) involves glutaryl-CoA dehydrogenase (decarboxylating) to crotonyl-CoA (trans-but-2-enoyl-CoA), hydration to (S)-hydroxybutanoyl-CoA, oxidization to acetoacetyl-CoA, and cleavage by a C-acetyltransferase to two acetyl-CoA.
- glutaryl-CoA-degradation: gcdH, ech, fadB and atoB
- Comment: In MetaCyc pathway glutaryl-CoA degradation (link), glutaryl-CoA is oxidized to (E)-glutaconyl-CoA and oxidatively decarboxylated to crotonyl-CoA (both by the same enzyme), hydrated to 3-hydroxybutanoyl-CoA, oxidized to acetoacetyl-CoA, and cleaved to two acetyl-CoA.
- putrescine-degradation: putrescine-to-GABA and GABA-degradation
- Comment: Gamma-aminobutyrate is a common intermediate.
- GABA-degradation: gabT and gabD
- Comment: GABA (4-aminobutanoate) is consumed by an aminotransferase (known as gabT or puuE), which forms succinate semialdehyde, and dehydrogenase gabD, which forms succinate.
- putrescine-to-GABA:
- patA and patD
- or puuA, puuB, puuC and puuD
- or puo and patD
- Comment: In pathway I or pathway V, putrescine aminotransferase (patA or spuC) forms 4-aminobutanal, and dehydrogenase patD forms GABA. In pathway II, putrescine is converted to GABA with glutamylated intermedates: puuA forms gamma-glutamyl-putrescine, an oxidase forms 4-(gamma-glutaminylamino)butanal, a dehydrogenase forms 4-(gamma-glutamylamino)butanoate, and a hydrolase releases glutamate and GABA. As part of pathway IV, putrescine oxidase (puo) forms 4-aminobutanal, which is probably converted to GABA by dehydrogenase patD.
- citrulline-transport:
51 steps (35 with candidates)
Or see definitions of steps
| Step | Description | Best candidate | 2nd candidate |
|---|
| AO353_03055 | ABC transporter for L-Citrulline, periplasmic substrate-binding component | BWI76_RS20340 | BWI76_RS19240 |
| AO353_03050 | ABC transporter for L-Citrulline, permease component 1 | BWI76_RS20330 | BWI76_RS19235 |
| AO353_03045 | ABC transporter for L-Citrulline, permease component 2 | BWI76_RS20325 | BWI76_RS19230 |
| AO353_03040 | ABC transporter for L-Citrulline, ATPase component | BWI76_RS20320 | BWI76_RS07590 |
| arcB | ornithine carbamoyltransferase | BWI76_RS03010 | BWI76_RS17500 |
| arcC | carbamate kinase | BWI76_RS07060 | BWI76_RS17520 |
| odc | L-ornithine decarboxylase | BWI76_RS24175 | BWI76_RS07195 |
| puuA | glutamate-putrescine ligase | BWI76_RS10710 | BWI76_RS00400 |
| puuB | gamma-glutamylputrescine oxidase | BWI76_RS10690 | |
| puuC | gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase | BWI76_RS10695 | BWI76_RS03865 |
| puuD | gamma-glutamyl-gamma-aminobutyrate hydrolase | BWI76_RS10705 | |
| gabT | gamma-aminobutyrate transaminase | BWI76_RS26375 | BWI76_RS14455 |
| gabD | succinate semialdehyde dehydrogenase | BWI76_RS05620 | BWI76_RS10695 |
| Alternative steps: |
| aruF | ornithine/arginine N-succinyltransferase subunit AruAI (AruF) | BWI76_RS11675 | |
| aruG | ornithine/arginine N-succinyltransferase subunit AruAII (AruG) | BWI76_RS11675 | |
| astC | succinylornithine transaminase | BWI76_RS11670 | BWI76_RS26000 |
| astD | succinylglutamate semialdehyde dehydrogenase | BWI76_RS11680 | BWI76_RS13425 |
| astE | succinylglutamate desuccinylase | BWI76_RS11690 | |
| atoB | acetyl-CoA C-acetyltransferase | BWI76_RS23445 | BWI76_RS01360 |
| citrullinase | putative citrullinase | | |
| davD | glutarate semialdehyde dehydrogenase | BWI76_RS05620 | BWI76_RS03865 |
| davT | 5-aminovalerate aminotransferase | BWI76_RS26375 | BWI76_RS14020 |
| ech | (S)-3-hydroxybutanoyl-CoA hydro-lyase | BWI76_RS13115 | BWI76_RS20455 |
| fadB | (S)-3-hydroxybutanoyl-CoA dehydrogenase | BWI76_RS01365 | BWI76_RS20455 |
| gcdG | succinyl-CoA:glutarate CoA-transferase | | |
| gcdH | glutaryl-CoA dehydrogenase | | |
| glaH | glutarate 2-hydroxylase, succinate-releasing (GlaH or CsiD) | | |
| lhgD | L-2-hydroxyglutarate dehydrogenase or oxidase (LhgD or LhgO) | | |
| ocd | ornithine cyclodeaminase | | |
| oraE | D-ornithine 4,5-aminomutase, beta (E) subunit | | |
| oraS | D-ornithine 4,5-aminomutase, alpha (S) subunit | | |
| ord | 2,4-diaminopentanoate dehydrogenase | | |
| orr | ornithine racemase | | |
| ortA | 2-amino-4-oxopentanoate thiolase, alpha subunit | | |
| ortB | 2-amino-4-oxopentanoate thiolase, beta subunit | | |
| patA | putrescine aminotransferase (PatA/SpuC) | BWI76_RS24630 | BWI76_RS14455 |
| patD | gamma-aminobutyraldehyde dehydrogenase | BWI76_RS13425 | BWI76_RS10695 |
| prdA | D-proline reductase, prdA component | | |
| prdB | D-proline reductase, prdB component | | |
| prdC | D-proline reductase, electron transfer component PrdC | | |
| prdF | proline racemase | | |
| PRO3 | pyrroline-5-carboxylate reductase | BWI76_RS06170 | BWI76_RS14970 |
| PS417_17590 | ABC transporter for L-Citrulline, periplasmic substrate-binding component | BWI76_RS07345 | BWI76_RS20340 |
| PS417_17595 | ABC transporter for L-Citrulline, permease component 1 | BWI76_RS20330 | BWI76_RS19235 |
| PS417_17600 | ABC transporter for L-Citrulline, permease component 2 | BWI76_RS20325 | BWI76_RS19230 |
| PS417_17605 | ABC transporter for L-Citrulline, ATPase component | BWI76_RS20320 | BWI76_RS10585 |
| puo | putrescine oxidase | BWI76_RS13080 | |
| put1 | proline dehydrogenase | BWI76_RS10795 | |
| putA | L-glutamate 5-semialdeyde dehydrogenase | BWI76_RS10795 | BWI76_RS07615 |
| rocA | 1-pyrroline-5-carboxylate dehydrogenase | BWI76_RS10795 | BWI76_RS07615 |
| rocD | ornithine aminotransferase | BWI76_RS26375 | BWI76_RS14020 |
Confidence: high confidence medium confidence low confidence
transporter – transporters and PTS systems are shaded because predicting their specificity is particularly challenging.
This GapMind analysis is from Sep 17 2021. The underlying query database was built on Sep 17 2021.
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About GapMind
Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory